Maternal–fetal conflict: Description and examples
The conflict hypothesis posits that the relationship between the mother and fetus has been shaped by natural selection 21. As the mother and fetus do not carry identical sets of genes, their evolutionary interests are not the same. Fetal genes will evolve to extract as much as possible from the mother to ensure their propagation (since these genes are not necessarily represented in future siblings), whereas maternal genes will evolve to promote the success of the current and future offspring to maximize their propagation. The conflict hypothesis predicts an evolutionary tug-of-war between maternal and fetal genomes, similar to virus-host interactions in which moves by one party are matched by countermoves of the other. Maternal–fetal conflict is manifest at a number of different organizational levels, from placental morphology and physiology to epigenetic marks on the genome. A few examples are described below:
Figure 2. Diagram showing development of the ovary and uterus, hormone levels (estradiol and progesterone), and key events (menstruation, ovulation, and decidualization) during the 28-day human menstrual cycle.
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Placental invasiveness and decidualization: The conflict hypothesis is invoked to explain why there is such a high degree of variation in invasiveness of the mammalian placenta, ranging from a superficial placenta that does not invade maternal tissues (epitheliochorial), to one that breaches the uterine epithelium (endotheliochorial), to one that breaches maternal blood vessels (hemochorial) (see 21). While increased invasiveness likely evolved for the benefit of the fetus, the decidualization reaction, which only occurs in mammals with invasive placentation, is thought to have evolved as a protective mechanism for the mother (see 15, 21). A number of decidual features point to its role in fetal restraint: decidual morphology consists of a continuous block of enlarged cells joined by tight junctions 15; the function of many decidual products is to inhibit the activity of invasive fetal proteins (e.g. see 16); and uterine NK cells induce apoptosis in invading trophoblast cells 59. Also, the occurrence of uncontrolled invasion during tubal and accrete pregnancies suggests that the maternal decidua is required for fetal restraint, as the decidual reaction in the fallopian tubes and at sites of accrete pregnancies is deficient and lacking NK cells 60, 61.
Placental and maternal hormones involved in glucose metabolism: The presence during pregnancy of very high levels of placental and maternal hormones involved in glucose metabolism suggests that an evolutionary escalation between maternal and fetal genomes has taken place. During the third trimester of pregnancy blood glucose increases after a meal, but it does not return to baseline in response to insulin as quickly as it does in the nonpregnant state. In addition, the maternal insulin response during pregnancy is exaggerated relative to the non-pregnant state. It has been argued that insulin is less effective during pregnancy because fetal hormones manipulate the maternal response to insulin to make more glucose available to the fetus. Placental lactogen, one of the most abundant placental hormones, has been cited as a likely candidate 21. In response to this fetal manipulation, the mother may have increased her production of insulin, evidenced by the peak levels of insulin during the third trimester (see 21 for more details).
Genomic imprinting: Conflict exists between genes expressed in the mother and fetus as described above, but it also occurs between maternally and paternally expressed genes in fetal tissues 21. Genomic imprinting of genes expressed in fetal tissues is evidence of conflict at this level. Under this hypothesis, paternally expressed alleles will enhance fetal/placental growth, and maternally expressed alleles in the fetus will restrict fetal/placental growth. Interestingly, most known imprinted genes are involved in fetal/placental growth and expressed in the placenta 62. The insulin and insulin-like-growth factor system provides good support for this hypothesis: IGF2, IGF2R, and INS, genes involved in placental and fetal growth and metabolism are imprinted and fit the pattern described above. For example, IGF2 is a gene expressed in the placenta that promotes trophoblast invasiveness, and is only expressed from the paternal allele 62.